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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Transplant Proc. Author manuscript; available in PMC 2010 July 28.
Published in final edited form as:
Transplant Proc. 1987 August; 19(4 Suppl 3): 61–62.
PMCID: PMC2911144
NIHMSID: NIHMS185761

Effect of OKT3 on Survival and Rate of Retransplantation

We have previously reported the results of our pilot randomized trial1,2 and our later extended series of 157 liver allograft recipients3,4 treated with the mouse antihuman T cell antibody OKT3 (Orthoclone OKT3, OrthoPharmaceutical Corporation, Raritan, NJ) for treatment of acute hepatic allograft rejection. An additional 93 liver transplant patients have been treated with OKT3 since the last investigation and were included in this study.

Methods

Between November 1984 and June 1986 250 hepatic allograft recipients received a course of OKT3. Follow-up data were available in all 250 patients until the beginning of March 1987, with a mean follow-up time of 432.9 ± 302.7 days. Baseline immunosuppression consisted of cyclosporine (Cs) and steroids. Clinical and histologic criteria leading to OKT3 therapy as well as principles of OKT3 therapy in conjunction with Cs and steroids have been extensively described previously.1,3,4

Analysis was performed using the previously described grouping scheme for allograft recipients.1 Briefly, in group 1 patients OKT3 treatment was started less than ten days postoperatively; in group 2 patients treatment was started ten days to three months postoperatively; and in group 3 patients treatment was started at greater than three months postoperatively.

Results

The average age of the 250 OKT3-treated patients was 28.4 ± 18.3 years. Eighty-seven patients were children (mean age, 6.3 ± 5.4 years), and 163 were adults (mean age, 40.2 ± 11.2 years). Two hundred twenty-one (88.4%) patients had their first graft, and the other 29 (11.6%) had undergone retransplantation before receiving OKT3 (Table 1).

Table 1
Graft Status at the Beginning of March 1987 and One-Year Survival in Liver Transplant Recipients Treated With OKT3

The response to OKT3 therapy was determined as survival of the allograft. At the beginning of March 1987, 146 (58.4%) patients treated with OKT3 had functioning allografts with an actuarial 1-year survival of 62.0%. Sixty-three patients (25.2%) needed retransplantation, and 41 patients (16.4%) died. Group 2 patients had superior results; 79 (71.8%) had functioning allografts, and the 1-year survival reached 74.3%. For comparative purposes additional data for all liver transplant recipients from August 1983 to June 1986 not treated with OKT3 were determined. Of 362 grafts 181 (50.0%) were functioning at the beginning of March 1987 with an actuarial 1-year survival of 53.3% (Table 1).

Discussion

In agreement with our previous study this investigation showed the efficacy of OKT3 in reversing acute hepatic allograft rejection. Our initial findings have also been verified by another center.5 The optimal response to OKT3 occurred in group 2 patients in whom cell-mediated rejection was the primary cause of postoperative liver allograft dysfunction. The less than optimal response rate in groups 1 and 3 reflects concomitant processes, ie, an element of coexisting ischemic injury and renal failure in group 1 and a degree of chronic rejection in group 3.

An important benefit of this drug was observed in patients who have historically done poorly. These patients typically present with hepatic allograft dysfunction in the early posttransplant period and usually have additional metabolic derangements, generally reflecting a precarious preoperative status. Such patients, especially if they present with an additional element of cellular rejection, appeared to benefit by a normalized graft function from OKT3 therapy.

Rejection is a major factor influencing the need for retransplantation.6 During the extended follow-up period the retransplantation rate appeared to diminish greatly in group 2 patients presenting primarily with cell-mediated rejection. The higher rate of retransplantation seen in group 1 and group 3 patients possibly reflects the inability of OKT3 to reverse the signs of concomitant disease disorders.

The decreased need for retransplantation is reflected in the survival of hepatic allografts. A significant increase in allograft survival was demonstrated. The major benefit was seen in group 2 patients, who had a superior 1-year graft survival (Table 1). In group 1 patients allograft survival approximated that in the historic control group.

These findings suggest that OKT3 has affected the overall success of liver transplantation with respect to allograft survival in patients with documented liver rejection. The normalization of survival curves in group 1 patients suggests that OKT3 also has a role in these critically ill patients as an added treatment for early rejection and/or prophylaxis in patients in whom Cs therapy must be handled cautiously. Thus OKT3, in conjunction with Cs and steroids, has improved the treatment of hepatic allograft rejection.

Acknowledgments

Supported by research grants from the Veterans Administration and by National Institutes of Health Grant No. AM-39961 B.H.M. is the recipient of Deutsche Forschungsgemeinschaft Research Fellow ship.

References

1. Fung JJ, Demetris AJ, Porter K, et al. Nephron. in press.
2. Starzl TE, Fung JJ. Transplant Proc. 1986;18:927.
3. Fung JJ, Markus BH, Gordon RD, et al. Transplant Proc. 1987;19 1:37. [PMC free article] [PubMed]
4. Esquivel CO, Fung JJ, Markus BH, et al. Transplant Proc. 1987;19:2443. [PMC free article] [PubMed]
5. Cosimi AB, Cho SI, Delmonico FL, et al. Transplant Proc. 1987;19:2431. [PubMed]
6. Shaw BW, Gordon RD, Iwatsuki S, et al. Semin Liver Dis. 1986;5:3943.